Fabrication of Self-Healing Hydrogels with On-Demand Antimicrobial Activity and Sustained Biomolecule Release for Infected Skin Regeneration

Microbial infection has been considered as one of the most critical challenges in bioengineering applications especially in tissue regeneration, which engenders severe threat to public health. Herein, a hydrogel performing properties of rapid self-healing, on-demand antibiosis and controlled cargo release was fabricated by a simple assembly of Fe complex as the cross-linker and hyaluronic acid as the gel network. This hydrogel is able to locally degrade and release Fe³⁺ to kill bacteria as needed because of hyaluronidase excreted by surrounding bacteria, resulting in efficient antibacterial activity against different types of bacteria. The sustained release property of certain types of growth factors was also observed from this hydrogel owing to its dense network. Moreover, this hydrogel could repeatedly heal itself in minutes because of the coordination interaction between Fe³⁺ and COOH, exhibiting good potential in bioengineering applications on the exposed tissue, where the materials are easily damaged during daily life. When topically applied onto damaged mouse skin with infection of Staphylococcus aureus, the hydrogel is able to inhibit microbial infections, meanwhile promoting cutaneous regeneration, which formed new skin with no inflammation within a 10 day treatment. These results demonstrate the potential application of this self-healing hydrogel for the integrated therapy of antibiosis and tissue regeneration.